Environmental Enrichment Induces Meningeal Niche Remodeling through TrkB-Mediated Signaling

Abstract

Neural precursors (NPs) present in the hippocampus can be modulated by several neurogenic stimuli, including environmental enrichment (EE) acting through BDNF-TrkB signaling. We have recently identified NPs in meninges; however, the meningeal niche response to pro-neurogenic stimuli has never been investigated. To this aim, we analyzed the effects of EE exposure on NP distribution in mouse brain meninges. Following neurogenic stimuli, although we did not detect modification of the meningeal cell number and proliferation, we observed an increased number of neural precursors in the meninges. A lineage tracing experiment suggested that EE-induced β3-Tubulin+ immature neuronal cells present in the meninges originated, at least in part, from GLAST+ radial glia cells. To investigate the molecular mechanism responsible for meningeal reaction to EE exposure, we studied the BDNF-TrkB interaction. Treatment with ANA-12, a TrkB non-competitive inhibitor, abolished the EE-induced meningeal niche changes. Overall, these data showed, for the first time, that EE exposure induced meningeal niche remodeling through TrkB-mediated signaling. Fluoxetine treatment further confirmed the meningeal niche response, suggesting it may also respond to other pharmacological neurogenic stimuli. A better understanding of the neurogenic stimuli modulation for meninges may be useful to improve the effectiveness of neurodegenerative and neuropsychiatric treatments.

The interaction between Environmental Enrichment and fluoxetine in inhibiting sucrose-seeking renewal in mice depend on social living condition

“…However, since the complexity of our behavioural paradigms and the three factors involved (EE, fluoxetine, living conditions), we cannot exclude that the behavioural outcomes observed might be the result of a complex interplay between other molecular mechanisms (Begni et al 2020 ; Eckert and Abraham 2013 ; Solinas et al 2021 ; van Praag et al 2000 ; Zorzin et al 2021 ). For instance, the different ‘EE experience’ due to the specific EE complexity and features used in social and isolated mice (2-level cage with littermates vs. new standard home cage without social component) may also represent another factor that could affect the efficacy of EE-fluoxetine combination in inhibiting sucrose-seeking.…”

The role of enriched environment in neural development and repair

“…At present, the research on the mechanism of EE affecting neurogenesis is still being explored. Early experiments have shown that EE can enhance the growth factors that promote neurogenesis, including brain-derived neurotrophic factor (BDNF; Zorzin et al, 2021 ), nerve growth factor (NGF; Pham et al, 1999 ), glial cell-derived neurotrophic factor (GDNF; Young et al, 1999 ), vascular endothelial cell growth factor (VEGF; Cao et al, 2004 ). A recent study suggests that EE and exercise can also enhance adult hippocampal neurogenesis through fibroblast growth factor receptor (FGFR), which induces the proliferation of stem and progenitor cells (Grońska-Pęski et al, 2021 ).…”

Enriched Environment and Exercise Enhance Stem Cell Therapy for Stroke, Parkinson’s Disease, and Huntington’s Disease

“…In experimental models, EE exerts a positive role in promoting regeneration, neurogenesis, and CNS remodeling. Exposure prevents relapse, enhances attention performance, reduces anxiety levels during development, prevents DNA methylation changes brought by aging, and enhances neurogenesis by increasing NPCs ( Korkhin et al, 2020 ; Zocher et al, 2021 ; Zorzin et al, 2021 ; Pintori et al, 2022 ). Similarly, exercise promotes positive effects on neurogenesis, trophic factor secretion, motor recovery following ischemia, cognitive and motor function, and neuroprotection ( Pang et al, 2006 ; Mang et al, 2013 ; Tsai et al, 2019 ).…”